This application proposes a renewal of a Midcareer Investigator Award in Patient-Oriented Research for Mary-Margaret Chren, MD, Professor of Dermatology at the University of California, San Francisco (UCSF). Dr. Chren's long-term career objectives are to perform rigorous research to improve the health of patients with skin diseases, and to use her research to develop first-rate investigators in patient-oriented research in skin diseases. This renewed award will build on her previous work and accomplish her immediate career objectives: first, to expand and complete the next phase of the Nonmelanoma Skin Cancer (NMSC) Cohort Study, a 10-year comparative effectiveness study of treatments for NMSC (the most common malignancy); second, to build on these findings to develop and perform a targeted multicenter clinical trial of treatments for NMSC; third, to use these research data as a substrate for the mentoring of clinician investigators in patient-oriented research; and fourth, to increase the scope of her mentoring activity by serving an expanded leadership role with the Mentorship Development Program of the UCSF Clinical & Translational Science Institute (CTSI). The proposed research will fill a gap in current knowledge about the comparative efficacy of the two most common treatments for NMSC, surgical excision and histologically-guided serial excision, or Mohs surgery. The research will undertake the incremental developmental steps to design and conduct a multicenter randomized controlled trial of excision and Mohs surgery for primary facial basal cell carcinomas (BCC). These steps include establishment of research, clinical, and stakeholder advisory groups, composition of study tools, drafting of study procedures, and pilot-testing of procedures. After infrastructure development, 1200 patients with primary facial BCC will be randomized to surgical excision or Mohs surgery. The primary outcome is tumor recurrence at five years; secondary outcome is skin-related quality of life. The proposed mentoring plan has three parts: didactic curricula, hands-on research, and career development; with the renewed award, didactic options will be fully integrated with CTSI's comprehensive program of highly-directed courses. This enhanced integration will be fostered by Dr. Chren's role as leader of the Mentor Evaluation Plan for the CTSI's Mentorship Development Program. Together, the Research Plan and Mentoring Plan provide a new five-year strategy that is directly relevant to the NIH and NIAMS missions of pursuing and applying knowledge to reduce disease burden, and training scientists to carry out such research.